Bioreactors are used to grow mammalian cell culture in which the cells produce an extracellular component, such as an antibody or recombinant protein. Bioreactors are also used for virus production. A separation process is performed in order to concentrate and purify the desired component from the bioreactor, which may, for example, be useful as a therapeutic or diagnostic agent. Bioreactors are complex mechanical devices that provide mainly the mixing and gasification of liquids to grow a target biological culture; this step is followed by several additional unit processes including the separation of cells, filtration to reduce the volume of nutrient medium, loading onto chromatography columns and several steps of purification. In recent years, there has been a raised awareness to produce many target biological products on a short turn around time, particularly as it relates to the products needed to combat terrorism-related needs; this also includes the need to quickly develop and manufacture vaccines and antibodies.
Current methods require large capital investment and lengthy and tedious processes to manufacture these products. There is a great unmet need for creating a manufacturing method to produce target biological products to reduce the manufacturing steps and reduce the cost of drug manufacturing and discovery.
A system that combines all steps in the manufacturing of target biological products, from growing cells to secrete them to separating the target biological product and purifying it within the same container that remains closed during the entire operation will change the way target biological drugs are developed and manufactured. This will be most suitable for situations where a product needs to be manufactured quickly such as in counter-terrorism operations as well as when protecting the public from epidemics since this system will allow a quick deployment of the manufacturing.
The aspect about combining the separation and purification of drugs within the bioreactor is novel and a disruptive technology. While the bioreactors are exclusively used for the purpose of growing cells, their role can be expanded to include other processes that can be completed within the bioreactor.
There is an unmet need to develop a manufacturing method for expressing and separating a target biological product from other components in the nutrient medium, combining the steps of expressing and separating within the bioreactor by binding the target biological product with a resin within a bioreactor, discarding the nutrient medium and eluting the target biological product as a concentrated solution; this will eliminate at least three steps in the separation and purification of target biological products—filtration or centrifugation to remove cell culture, perform ultrafiltration for volume reduction, and purification of target biological product by selective elution from the bioreactor; the last use makes the bioreactor a chromatography column.
Other unattended problems in the manufacture of biological drugs is in the need to remove undesirable metabolites from a bioreactor to enhance the growth of cell culture; a method for removing these components will improve the yield of production.
Another unattended problem in the manufacture of biological drugs is in the purification step wherein a binding resin is loaded on to a chromatography column and is often wasted in the process of loading. There is a need to device an assembly that would totally contain the binding resin in a sheath that is disposed in a chromatography column reducing the losses incurred in the loading.